Current Diabetes Reports

, 19:102 | Cite as

Pharmacological Modulation of Ghrelin to Induce Weight Loss: Successes and Challenges

  • Martha A. Schalla
  • Andreas StengelEmail author
Obesity (KM Gadde, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Obesity


Purpose of Review

Obesity is affecting over 600 million adults worldwide and has numerous negative effects on health. Since ghrelin positively regulates food intake and body weight, targeting its signaling to induce weight loss under conditions of obesity seems promising. Thus, the present work reviews and discusses different possibilities to alter ghrelin signaling.

Recent Findings

Ghrelin signaling can be altered by RNA Spiegelmers, GHSR/Fc, ghrelin-O-acyltransferase inhibitors as well as antagonists, and inverse agonists of the ghrelin receptor. PF-05190457 is the first inverse agonist of the ghrelin receptor tested in humans shown to inhibit growth hormone secretion, gastric emptying, and reduce postprandial glucose levels. Effects on body weight were not examined.


Although various highly promising agents targeting ghrelin signaling exist, so far, they were mostly only tested in vitro or in animal models. Further research in humans is thus needed to further assess the effects of ghrelin antagonism on body weight especially under conditions of obesity.


Antagonist Ghrelin-O-acyl transferase GOAT Growth hormone Inverse agonist Obesity 



Adrenocorticotropic hormone


Non-CNS penetrant inverse agonist 22


CNS penetrant inverse agonist 38


Body mass index


Compound B


Compound D


Diet-induced obesity


Growth hormone


Growth hormone–releasing peptide-2


Growth hormone–releasing peptide 6


Growth hormone secretagogue receptor




Ghrelin receptor








RNA Spiegelmer


World Health Organization.


Author Contributions

M.S. wrote the first draft of the paper, and A.S. thoroughly reviewed the manuscript; both authors finalized the manuscript.

Funding Information

This work was supported by funding of the German Research Foundation (STE 1765/3-2) and Charité University Funding (UFF 89/441-176, A.S.).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Authors and Affiliations

  1. 1.Charité Center for Internal Medicine and DermatologyCharité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthBerlinGermany
  2. 2.Department of Psychosomatic Medicine and PsychotherapyMedical University Hospital TübingenTübingenGermany

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